Andi Husni TANRA

Professor of Anesthesiology

Department of Anesthesiology, IC and Pain Management

Faculty of Medicine Hasanuddin University

Makassar

Introduction to Pain

2

Poisons

Tissue damage

Release of mediators

Stimulation of nociceptors

Transmission to CNS

What is pain?

How do we feel pain? In normal situation!

Noxious

stimulus

Nociceptors

Transduction

Conduction

Modulation

Transmission Pain

Perception

Stimulate

Regarding to the function of pain.

TWO KINDS OF PAIN

*Good Pain, is an alarm symptom, tell us that something

wrong in our body Acute Pain, pain with nociception

(nociceptive pain). alarm protection.

Disini nyeri seperti bel rumah bunyi kl ada tamu

*Bad pain, is a disease entity, no nociception,

nothing wrong but patient feel severe pain makes patient

suffering Chronic Pain.

Disini nyeri seperti bel rumah yg korsleting tidak ada

tamu tapi bel rumah bunyi terus.

The word “pain” derives from latin word “poena” meaning“punishment”.

congenital insensitivity to pain ( chennelopathy)

CHRONIC PAIN vs ACUTE PAIN

Chronic pain is misleading or over simplistic. The key distinction between acute & chronic is not the DURATION of pain, but

chronic pain is pain that PERSIST

BEYOND HEALING BEYOND NOCICEPTION BEYOND EXPECTION

DIFFICULT TO TREAT. (symptom is disproportionate) NO BIOLOGICAL MEANING. IT CAUSED SUFFERING AND BEHAVIOR CHANGES Bad Pain

Phantom Limb Pain After limb amputation

Two type of pain syndrome

Stump pain

Phantom pain

The incidence of phantom pain varies

from 50% - 85%

About 40% of amputees having

severe phantom pain

ACUTE PAIN

Acute pain is pain that

Associated with tissue damage or nociception.

Has biological meaning.

Has tendency to recover as nociception is vanished.

Symptom is slightly proportionate.

It caused protection for further damage Good

Pain

Prototipe dari acute pain postoperative pain

Clinical Features

of Postoperative Pain

ALLODYNIA

HYPERALGESIA

PATHOPHYSIOLOGICAL PAIN

(CLINICAL PAIN)

Vanished after

healing process finished

So pain, between acute & chronic pain

is absolutely different ;

Different in etiology

Different in pathophysiology

Different in diagnosis

Different in treatment

HAROLD MERSKEY (psychiatrics) proposed

definition of pain, which was accepted by

IASP (International Association for Study of Pain 1979)

PAIN IS “AN UNPLEASANT SENSORY AND EMOTIONAL EXPERIENCE

ASSOCIATED WITH ACTUAL OR POTENTIAL TISSUE DAMAGE, OR

DESCRIBED IN TERM OF SUCH DAMAGE”

Nyeri adalah perasaan sensorik dan emosional yang tidak menyenangkan

akibat adanya kerusakan jaringan yang nyata atau yang berpotensi rusak

atau tergambarkan seperti kerusakan tersebut.

The problem lies in the word unpleasant.

Pain is more than unpleasant.

The great merits of this definition

1. Pain is unpleasant sensory and unpleasant emotional

experience. Kata tidak menyenangkan harus ada nyeri

2. Pain usually associated with actual tissue damage

Nociceptive pain or acute pain PAIN WITH

NOCICEPTION

3. Pain may occur with potential tissue damage (noxious

stimulus) PHYSIOLOGICAL PAIN withdrawal- reflex.

4. Pain is described in term of such damage, although nothing

wrong in his/her body but patient feel severe pain,

PAIN WITHOUT NOCICEPTION CHRONIC PAIN

Classification of Pain

Based on Duration: Acute and Chronic.

Based on Clinical Context:

• Postsurgical

• Malignancy related

• Neuropathic

• Degenerative .

Based on Organ

- Headache

-Pelvic pain

-Lowback pain Based on Pathophysiological -Mechanism :

- Nociceptive pain

- Neuropathic pain

Most Accepted Classification:

Nociceptive pain = tissue injury

(Acute pain) Somatic Pain

Visceral Pain

Neuropathic pain = nerve injury

(chronic Pain)

Mechanism of Nociceptive pain.

Noxious

stimulus

Nociceptors

Transduction

Conduction

Modulation

Transmission Pain

Perception

Stimulate

Nociceptive Pain is pain that generated

from nociceptors. Nyeri yang dibangkitkan

dimulai dari nosiseptor

1. NOCICEPTORS

What is a nociceptor? reseptor nyeri

Nociceptors are peripheral sensory neurons that respond selectively to noxious stimuli (Stimulus kuat).

Or A number of receptors/channels that sense damage

VR1 - vanilloid receptor family ASICs - respond to low pH P2X receptors - respond to ATP TRPs receptors – respond temp. Chemical sensors - prostaglandins,

Diciptakan Tuhan guna melindungi diri kita dari bahaya.

TRPVs ASICs TRPs P2X

capsaicin

H+

PGs

EPs

cold warm ATP

COX1/2

ATP

heat

Na+, K+,

Ca2+

channels

DRG

C-fibre

Tissue damage and pain in the periphery

Mechanical?

2. SENSORY NERVE

AFFERENT

Sensory afferent n.f.

connecting receptors to

the CNS

(Centripetal)

Motor afferent n.f. is

connecting CNS to

muscle or gland

(centrifugal).

Sensory Nerve

Afferent

Anatomy of peripheral sensory nerve fibers

A

A C

Dorsal Horn

Dorsal root

ganglion

Peripheral sensory

Nerve fibers

A

A

C

Large

fibers

Small

fibers

Two sensory afferent neurons 1. Large myelinated A fibers, very fast conduction velocity. Respond to

innocuous stimuli

2. Small myelinated A & C unmyelinated fibers, have slow conduction

velocity. Respond to noxious stimuli

Modified by AHT

A

A

C Lateral

Nucleus

proprius

Marginal layer Substantia

gelatinosa Medial

Afferent Synaptic in DHN

Characteristic of A and C-fiber

Polimodal

Nociceptors

A Fiber Rapid Conduction

C-Fiber Slow Conduction

Mechano Thermal

Nociceptors

Glu

First Pain

Secound

Pain

Glu

sP

Two distinct responses to a noxious stimulus

FIRST PAIN and SECOUND PAIN

• First pain: sharp and pricking,

well-localised and brief.

Responded by

mechanoreceptors , conveyed

by Ad fiber.

• Second pain: dull and diffuse

and prolonged . Responded by

polimodal nociceptors ,

conveyed by C fiber C Fiber

A Fiber

First Pain

Secound Pain

Modified by AHT

Although in normal condition A fiber does not response to

noxious stimuli, but it plays a big role in NORMAL

SENSATION.

The Role of A fiber

Without A fiber, any noxious stimuli will perceive

as BURNING PAIN (TN, HZ)

A

1. TRANSDUCTION 2. CONDUCTION

Role of nociceptors and

primary afferent neurons

are:

Process whereby noxious

stimuli are translated

into electrical activity at

the sensory endings of

nerve Heat

Chemical

TRANSDUCTION

TRANSDUCTION

Pressure

1. TRANSDUCTION PROCESS (NOCICEPTORS ACTIVATION and CONDUCTION)

Action Potential

Na+

Ca++

TRP Peptides-

sP, CCK,

CGRP

Ca++ TRP

Generator

Potential

Traumatic

Mediators-

K+, H+,

ATP,PGE

Neural

Mediators-

Epine,

Norepine

Local &

Vescular

Mediators-

Bradykinin,

Cytokines

Histamine,

5HT.

In Creased

Synthesis

Pro

Inflammatory

Cytocaines

-(IL) 1

-IL-6

Modified by AHT

R. Sinatra 2007

“Noxious Soup”

Tissue

Injury

TRP (Transient Receptor Potential) Ion

Channel is a Transducer molecules.

K+ K+

Ca2+

Na+

1. Transduction

4. Transmission 2. Spike Initiation

3. Propagation (conduction)

Modified Meliala, 2006

Transduction and Conduction Process

Mechanical

Thermal

Chemical

Transduction

Conduction

Modulation

Transmission

Persepsion

Neuron I

Neuron II

Neuron III

Modified by AHT

3. MODULATION in DHN

Lehmann, K. A.: From the first stimulus to pain memory. UN. Cologne, 2000

Dorsal Horn neurons of SC Plays a big role in pain perception

Is the first gate to control pain.

Nociception (Pain) is born in DHN

36

Modulation in Dorsal Horn Neurons

Done by Descending neurons & Interneurons

37 Modulation at DH

Postsynaptic

Opioid

Receptors

(-)

(+)

Glutamate

Receptors

Enkephalinergic

Interneuron

(Inhibitory)

Descending

Enkephalinergic

Fiber (Inhibitory)

Presynaptic Opioid

Receptors

(-)

Primary

Nociceptive

Fiber

Spinal Sensory

Neuron

ENK ENK

ENK

ENK

SITES OF ENKEPHALIN BINDING IN SPINAL CORD.

PLAYED BY DESCENDING INHIBITORY AND INTRNEURON INHIBITORY FIBER

Modified by AHT

Modulation

Peranan Modulasi dalam kehidupan

Peran modulasi inilah yang membuat persepsi nyeri menjadi sangat subyektif.

Ransangan yang sama dirasakan berbeda oleh tiap orang. ( latar belakang yang berbeda)

Bahkan R yang sama dirasakan berbeda oleh orang yg sama kr kondisi emasionalnya berbeda.

Suatu Nyeri mamiliki 3 dimensi;

1. Cognitive ( dimana dan intesitas nyeri)

2. Affective ( arti dari suatu nyeri)

3. Emotional ( atensi thp nyeri )

Pain is very Subjective

feeling

Pain has multidimensional experience

1. sensory – discriminative

Identifies the intensity, type and location of pain

2. Affective – motivational

Assessing the injury the meaning of injury

3. Emotional – behavioral component

Attention, mood and behavioral due to pain

1. MODULATION 2. TRANSMISSION

Thus, the role of DHN, is the place

where interaction between afferent

ascendern input and descedern

input.

4. ASCENDING PATHWAYS

Spinothalamic

tract Peripheral

nerve

Dorsal Horn

Dorsal root

ganglion

Pain

Medulation

Ascending

input

Descending

modulation

Peripheral

nociceptors

Trauma

Adapted from Gottschalk A et al. Am Fam Physician. 2001;63:1981, and Kehlet H et al. Anesth Analg. 1993;77:1049.

Conduction

Modified by AHT

Transduction

5. DESCENDING MODULATING

PATHWAYS

Descending

pathways

Ascending

pathways

Brain is a huge

Pharmacetucal

Factory.

Dorsal homs Opioids

NRM LC

PAG

Cortex

Opioids

Descending Modulatory

Systems

5-HT - - Enkephalin - Norepinephrine

Modified by AHT

Begitu kuatnya proses

Desendern sehingga orang ini

seperti tidak punya Otak.

Perception is on the brain, so

No brain no pain.

Pain

Perception Brain

Noxious perception?

A number of theories:

1. Specificity theory by Descartes

(16 century)

2. Gate control theory by Melzack

and Wall (i965)

3. Sensitization theory by Woolf et

al (1990 an)

How pain perception is processed, still obscured, and Where pain perceptions in the brain still unclear.

Limbic Cortex

Sensory Cortex

Thalamus

SS

SS

Pain was faithfully

transmitted from

periphery to brain

1. Specificity theory

Descartes (17th Century)

Modified by AHT

NO BRAIN, NO PAIN

2.GATE CONTROL THEORY by MELZACK and Wall

Ascending Action

System

Large

fibers

Central

Control

Descending

Modulation

Small

fibers Dorsal Horn “Gate”

The Gate control theory of pain processing. T = Second-order transmission cell; SG = substantia

gelatinosa cell.

Modified by AHT

Prof. Hyodo

Prof. Hyodo

3.Sensitization theory , by Woolf et in 1990

:After the tissue injury, sensitization in the

periphery and centrally ns is occurred.

HYPERALGESIA : RANGSANG KUAT YANG NORMAL

DIRASAKAN NYERI KINI LEBIH NYERI

ALLODYNIA: RANGSANG LEMAH YANG NORMAL TIDAK

TERASA NYERI KINI TERASA NYERI

After tissue damage it occurs peripheral

and central sensitization

Increasing Stimulus Intensity

Stimulus response alteration observed with hyperalgesia

No Pain

Allodynia

“Hyperalgesia” Normal

Response

Worst Pain

Tissue Injury Arachidonic Acid

Prostaglandine

Pain

CycloOxyganase

Enzym

-Aspirin

-Ibuprophen

-Ketoprophen

-Ketorolac

-Etc.

Nonsteroidal Anti Inflammatory Drugs (NSAID)

- Paracetamol not NSAID

Anti

Primary hyperalgesia

Secondary hyperalgesia

(allodynia)

So, there are three

possibilities how do

we feel pain.

1. Nociception with Pain

Pain

CNS

Nociception exp. normal situation

Noxious stimulus with Pain

Inhibition

Excitation

Modulation

Pain

CNS

Nociception Noxious stimulus without Pain

Inhibition

Excitation

Example:

Stress Induced Analgesia

X

Modulation

2. Nociception without pain

Pain

CNS

Nociception Pain without noxious stimulus

Inhibition

Excitation

Example: Phantom Pain

Neurophatic Pain

X

Modulation

3. Pain without nociception

New concepts of

ACUTE PAIN TREATMENT

Modify by AHT

Ketamin

Acetaminophen

Transduction

Transduction Modulation

Perception

Transmission

Modulation

Target Point of Analgesic Agents

SEKIAN Terima Kasih Banyak

Semoga Ada Manfaatnya